The overarching theme of this proposal is "Impact of Tumor Heterogeneity on Cancer Progression". The Theoretical Component has developed, over the years, a suite of mathematical and computational models based on state-of-the-art techniques, with the goal of spanning a range of temporal and spatial resolution at the cellular scale. Our modelers and experimentalists are in continuous contact to facilitate data incorporation into models. Some theoretical scientists are specifically dedicated to data analysis prior to model integration. Special additions to this Component are the Altschuler/Wu group, leaders in experimental/theoretical approaches to trait heterogeneity, and evolution scientists.